title: Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction.
abstract: We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries.
authors.affiliation: Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Paul
authors.initials: P
authors.lastname: Kosterin
authors.forename: Brian M
authors.initials: BM
authors.lastname: Salzberg
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Milovanova
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000633:toxicity*; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D019570:Inhalation Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity*; D014652:Vascular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D052638:Particulate Matter; D002248:Carbon Monoxide
keywords: Action potential; Leukocytes; Neurohypophysis; Neutrophil activation; Platelets; Vascular leak